The human gut microbiome produces and consumes a variety of compounds that interact with the host and impact health. Succinate is of particular interest as it intersects with both host and microbiome metabolism. However, which gut bacteria are most responsible for the consumption of intestinal succinate is poorly understood. We build upon an enrichment-based whole fecal sample culturing approach and identify two main bacterial taxa that are responsible for succinate consumption in the human intestinal microbiome, Phascolarctobacterium and Dialister. These two taxa have the hallmark of a functional guild and are strongly mutual exclusive across 21,459 fecal samples in 94 cohorts and can thus be used to assign a robust “succinotype” to an individual. We show that they differ with respect to their rate of succinate consumption in vitro and that this is associated with higher concentrations of fecal succinate. Finally, individuals suffering from inflammatory bowel disease (IBD) are more likely to have the Dialister succinotype compared to healthy subjects. We identified that only two bacterial genera are the key succinate consumers in human gut microbiome, despite the fact that many more intestinal bacteria encode for the succinate pathway. This highlights the importance of phenotypic assays in functionally profiling intestinal microbiota. A stratification based on “succinotype” is to our knowledge the first function-based classification of human intestinal microbiota. The association of succinotype with IBD thus builds a bridge between microbiome function and IBD pathophysiology related to succinate homeostasis.

The human gut microbiome produces and consumes a variety of compounds that interact with the host and impact health. Succinate is of particular interest as it intersects with both host and microbiome metabolism. However, which gut bacteria are most responsible for the consumption of intestinal succinate is poorly understood. Here, we build upon an enrichment-based whole fecal sample culturing approach and identify two main bacterial taxa that are responsible for succinate consumption in the human intestinal microbiome, Phascolarctobacterium and Dialister . These two taxa have the hallmark of a functional guild and are strongly mutual exclusive across over 20,000 fecal samples in nearly 100 cohorts and can thus be used to assign a robust ‘succinotype’ to an individual. We show that they differ with respect to their rate of succinate consumption in vitro and that this is associated with higher concentrations of fecal succinate. Finally, individuals suffering from inflammatory bowel disease (IBD) are more likely to have the Dialister succinotype compared to healthy subjects. The functionally meaningful classification of human intestinal microbiota based on ‘succinotype’ thus builds a bridge between microbiome function and IBD pathophysiology related to succinate.

Triterpene glycosides (TTGs) are characteristic constituents of Cimicifuga racemosa extract Ze 450 and may contribute to its pharmacological effects in the treatment of menopausal symptoms. This exploratory study investigated their gastrointestinal stability, transformation during incubation with human fecal microbiota, and potential effects on microbial community composition and short-chain fatty acid (SCFA) production. The stability of 23-epi-26-deoxyactein was assessed during simulated oral and gastric digestion using the INFOGEST protocol. Microbiota-associated biotransformation of actein, 23-epi-26-deoxyactein, cimigenol-3-β-D-xyloside, and cimigenol-3-α-L-arabinoside was subsequently examined during 48 h anaerobic ex vivo cultivation with fecal microbiota from eight female donors. 23-Epi-26-deoxyactein remained largely stable during simulated oral and gastric digestion. During fecal incubation, all investigated TTGs were depleted and the corresponding aglycones were detected. Quantification of the 23-epi-26-deoxyactein aglycone revealed marked donor-dependent differences, indicating substantial interindividual variability in TTG biotransformation. Individual TTGs had little effect on microbial community composition or SCFA profiles, whereas Ze 450 induced a small but significant shift in overall community structure without substantially affecting SCFA production. These findings demonstrate extensive microbiota-mediated TTG deglycosylation and highlight marked interindividual variability in TTG metabolism, providing a rationale for further investigation of microbiome-dependent differences in the pharmacological fate of Ze 450.